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MedKoo Cat#: 200291 | Name: Tucatinib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tucatinib, also known as Irbinitinib, ARRY-380 and ONT-380, is an potent HER2 inhibitor. Tucatinib exhibits potent inhibitory activity against HER2 kinase with an IC₅₀ of 8 nM. In HER2-overexpressing cancer cell lines (e.g., BT-474, SK-BR-3), Tucatinib effectively inhibits cell proliferation with IC₅₀ values in the low nanomolar range. It also downregulates HER2 phosphorylation and signaling through downstream pathways such as PI3K/AKT and MAPK/ERK

Chemical Structure

Tucatinib
Tucatinib
CAS#937263-43-9

Theoretical Analysis

MedKoo Cat#: 200291

Name: Tucatinib

CAS#: 937263-43-9

Chemical Formula: C26H24N8O2

Exact Mass: 480.2022

Molecular Weight: 480.53

Elemental Analysis: C, 64.99; H, 5.03; N, 23.32; O, 6.66

Price and Availability

Size Price Availability Quantity
5mg USD 65.00 Ready to Ship
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
1g USD 750.00 Ready to ship
5g USD 2,150.00 Ready to ship
10g USD 3,450.00 Ready to ship
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Related CAS #
937263-43-9 937265-83-3 (ARRY-380 analog)
Synonym
ARRY380; ARRY 380; ARRY-380; ONT380; ONT 380; ONT-380. Irbinitinib; Tucatinib.
IUPAC/Chemical Name
N6-(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)-N4-(3-methyl-4-((1,2,4)triazolo(1,5-a)pyridin-7-yloxy)phenyl)quinazoline-4,6-diamine
InChi Key
SDEAXTCZPQIFQM-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)
SMILES Code
CC1=CC(NC2=C3C=C(NC4=NC(C)(C)CO4)C=CC3=NC=N2)=CC=C1OC5=CC6=NC=NN6C=C5
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Note: As of 9/1/2015, there are several vendors listed ARRY-380 as a wrong structure.
Biological target:
HER2 inhibitor with an IC50 of 8 nM
In vitro activity:
To investigate the effects of tucatinib on leukemia cells, MTT assays were subsequently performed to determine the cytotoxicity of tucatinib on 2 leukemia cell lines. As shown in Fig. 1B and C, >80% of the HL60/ABCG2 and K562/ABCG2 ABCG2-overexpressing cell lines, and their parental cell lines, HL60 and K562, survived 0.4 µM tucatinib treatment. Therefore, 0.4 µM tucatinib was selected as the maximum working concentration for further experiments. Subsequently, whether tucatinib, at various concentrations, could increase the sensitivity of ABCG2-overexpressing leukemia drug resistant cells to mitoxantrone and topotecan was investigated. As shown in Tables I and andII,II, the ABCG2-overexpressing HL60/ABCG2 and K562/ABCG2 cell lines showed higher IC50 values to the ABCG2 substrates, mitoxantrone and topotecan compared with that in their parental cell lines, respectively. In the presence of 0.1 and 0.2 µM tucatinib, there was a significant increase in sensitivity of the cell lines to the two drugs. Tucatinib (0.4 µM) further increased the sensitivity of leukemia cells to the two drugs in both the ABCG2-overexpressing HL60/ABCG2 and K562/ABCG2 cell lines, and its efficacy was comparable to that of the known ABCG2 inhibitor, FTC (2.5 µM). Conversely, tucatinib did not significantly alter the IC50 value of cisplatin in all the leukemia cell lines, which is a non-ABCG2 substrate. Taken together, these results suggested that tucatinib may significantly sensitize ABCG2-overexpressing leukemia cells to become anti-neoplastic. Reference: Oncol Rep. 2021 Mar; 45(3): 1142–1152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859976/
In vivo activity:
The ability of tucatinib to prevent tumor cell growth in vivo was investigated in HER2+ breast and gastric cancer CDX xenograft models. Female immunocompromised mice implanted with BT-474 cells were treated with tucatinib and evaluated for response. Mice treated with tucatinib exhibited tumor growth delay at doses of 25 or 50 mg/kg tucatinib administered orally every day. This effect was similar to mice treated with trastuzumab monotherapy (Fig. 4A). In contrast, mean tumor volume (MTV) increased > 4-fold in mice treated with vehicle (Fig. 4A). Reference: Mol Cancer Ther. 2020 Apr;19(4):976-987. https://mct.aacrjournals.org/content/19/4/976.long
Solvent mg/mL mM
Solubility
DMF 1.0 2.08
DMSO 49.0 101.97
DMSO:PBS (pH 7.2) (1:2) 0.3 0.69
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 480.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Jing W, Zhou M, Chen R, Ye X, Li W, Su X, Luo J, Wang Z, Peng S. In vitro and ex vivo anti‑tumor effect and mechanism of Tucatinib in leukemia stem cells and ABCG2‑overexpressing leukemia cells. Oncol Rep. 2021 Mar;45(3):1142-1152. doi: 10.3892/or.2020.7915. Epub 2020 Dec 30. PMID: 33650639; PMCID: PMC7859976. 2. Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, Forero-Torres A, Peterson S. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol Cancer Ther. 2020 Apr;19(4):976-987. doi: 10.1158/1535-7163.MCT-19-0873. PMID: 32241871.
In vitro protocol:
1. Jing W, Zhou M, Chen R, Ye X, Li W, Su X, Luo J, Wang Z, Peng S. In vitro and ex vivo anti‑tumor effect and mechanism of Tucatinib in leukemia stem cells and ABCG2‑overexpressing leukemia cells. Oncol Rep. 2021 Mar;45(3):1142-1152. doi: 10.3892/or.2020.7915. Epub 2020 Dec 30. PMID: 33650639; PMCID: PMC7859976.
In vivo protocol:
1. Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, Forero-Torres A, Peterson S. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol Cancer Ther. 2020 Apr;19(4):976-987. doi: 10.1158/1535-7163.MCT-19-0873. PMID: 32241871.
1: Bartsch R, Pérez-García JM, Furtner J, Berghoff AS, Marhold M, Starzer AM, Hughes M, Kabraji S, Sammons S, Anders C, Murthy RK, Van Swearingen AED, Pereslete A, Gion M, Vaz Batista M, Braga S, Pinto PBC, Sampayo-Cordero M, Llombart-Cussac A, Preusser M, Cortés J, Lin NU. Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis. ESMO Open. 2025 Jan 3;10(1):104092. doi: 10.1016/j.esmoop.2024.104092. Epub ahead of print. PMID: 39754978. 2: Strickler JH, Bekaii-Saab T, Cercek A, Heinemann V, Nakamura Y, Raghav K, Siena S, Tabernero J, Van Cutsem E, Yoshino T, Ramos J, Guan X, Andre T. MOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol. 2024 Dec 26:1-9. doi: 10.1080/14796694.2024.2441101. Epub ahead of print. PMID: 39723627. 3: Alzahrani AK, Imran M, Alshrari AS. Investigating the impact of SOD1 mutations on amyotrophic lateral sclerosis progression and potential drug repurposing through in silico analysis. J Biomol Struct Dyn. 2024 Dec 14:1-16. doi: 10.1080/07391102.2024.2439577. Epub ahead of print. PMID: 39673548. 4: Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Correction: Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Dec 11. doi: 10.1007/s40262-024-01458-0. Epub ahead of print. Erratum for: Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. PMID: 39661316. 5: Podder V, Ranjan T, Gowda M, Camacho AM, Ahluwalia MS. Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review. Curr Neurol Neurosci Rep. 2024 Dec 3;25(1):6. doi: 10.1007/s11910-024-01388-1. PMID: 39625633. 6: Ayub MA, Tyagi AR, Srivastava SK, Singh P. Quantum DFT analysis and molecular docking investigation of various potential breast cancer drugs. J Mater Chem B. 2024 Dec 18;13(1):218-238. doi: 10.1039/d4tb01803f. PMID: 39545283. 7: Avelino ARM, Pulipati S, Jamouss K, Bhardwaj PV. Updates in Treatment of HER2-positive Metastatic Breast Cancer. Curr Treat Options Oncol. 2024 Dec;25(12):1471-1481. doi: 10.1007/s11864-024-01277-2. Epub 2024 Nov 9. PMID: 39520520. 8: Guglielmi G, Zamagni C, Del Re M, Danesi R, Fogli S. Targeting HER2 in breast cancer with brain metastases: A pharmacological point of view with special focus on the permeability of blood-brain barrier to targeted treatments. Eur J Pharmacol. 2024 Dec 15;985:177076. doi: 10.1016/j.ejphar.2024.177076. Epub 2024 Oct 30. PMID: 39486766. 9: Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5. Erratum in: Clin Pharmacokinet. 2024 Dec 11. doi: 10.1007/s40262-024-01458-0. PMID: 39368039; PMCID: PMC11522094. 10: Sankarapandian V, Rajendran RL, Miruka CO, Sivamani P, Maran BAV, Krishnamoorthy R, Gangadaran P, Ahn BC. A review on tyrosine kinase inhibitors for targeted breast cancer therapy. Pathol Res Pract. 2024 Nov;263:155607. doi: 10.1016/j.prp.2024.155607. Epub 2024 Sep 25. PMID: 39326367. 11: Mahtani R, Harpalani N, Yan F, Phiel K, Kovalenko I. Expanding treatment options for patients with HER2+ metastatic breast cancer with margetuximab plus chemotherapy: a case report series. Front Oncol. 2024 Aug 16;14:1419246. doi: 10.3389/fonc.2024.1419246. PMID: 39220641; PMCID: PMC11362812. 12: Sun K, Wang X, Zhang H, Lin G, Jiang R. Management and Mechanisms of Diarrhea Induced by Tyrosine Kinase Inhibitors in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer. Cancer Control. 2024 Jan- Dec;31:10732748241278039. doi: 10.1177/10732748241278039. PMID: 39159918; PMCID: PMC11334140. 13: Amrell L, Bär E, Glasow A, Kortmann RD, Seidel C, Patties I. Enhanced anti- tumor effects by combination of tucatinib and radiation in HER2-overexpressing human cancer cell lines. Cancer Cell Int. 2024 Aug 6;24(1):277. doi: 10.1186/s12935-024-03458-3. PMID: 39107782; PMCID: PMC11302197. 14: Chen Y, Liu C, Wen X, Wang C, He J. Treatment of HER2-Positive Breast Cancer with Brain Metastases Using Anlotinib and Trastuzumab Deruxtecan: A Case Report. Int J Womens Health. 2024 Jul 29;16:1277-1283. doi: 10.2147/IJWH.S472628. PMID: 39100110; PMCID: PMC11296372. 15: Liu HN, Zhu Y, Chi Y, Zhang Y, Li X, Wen W, Shan LS, Wang YT, Dai B. Synthetic routes and clinical application of Small-Molecule HER2 inhibitors for cancer therapy. Bioorg Chem. 2024 Oct;151:107653. doi: 10.1016/j.bioorg.2024.107653. Epub 2024 Jul 16. PMID: 39024803. 16: Pellerino A, Davidson TM, Bellur SS, Ahluwalia MS, Tawbi H, Rudà R, Soffietti R. Prevention of Brain Metastases: A New Frontier. Cancers (Basel). 2024 Jun 4;16(11):2134. doi: 10.3390/cancers16112134. PMID: 38893253; PMCID: PMC11171378. 17: Conte P, Ciruelos E, Curigliano G, De Laurentiis M, Del Mastro L, Gennari A, Llombart A, Martìn M, Poggio F, Prat A, Puglisi F, Saura C. "Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper". Breast. 2024 Aug;76:103742. doi: 10.1016/j.breast.2024.103742. Epub 2024 May 16. PMID: 38772190; PMCID: PMC11134910. 18: Rodriguez GF, Shah A, Maderal AD. Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer. Breast Dis. 2024;43(1):61-64. doi: 10.3233/BD-230053. PMID: 38578876; PMCID: PMC11091628. 19: Frenel JS, Zeghondy J, Guérin-Charbonnel C, Mailliez A, Volant E, Poumeaud F, Patsouris A, Arnedos M, Bailleux C, Cabal J, Galland L, de Nonneville A, Guiu S, Dalenc F, Pistilli B, Bachelot T, Pierga JY, Le Du F, Bocquet F, Larrouquere L, Loirat D. Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer. JAMA Netw Open. 2024 Apr 1;7(4):e244435. doi: 10.1001/jamanetworkopen.2024.4435. PMID: 38568692; PMCID: PMC10993071. 20: Robinson HR, Messersmith WA, Lentz RW. HER2-Positive Metastatic Colorectal Cancer. Curr Treat Options Oncol. 2024 May;25(5):585-604. doi: 10.1007/s11864-024-01183-7. Epub 2024 Mar 28. PMID: 38539034.

1. Conlon NT, Kooijman JJ, van Gerwen SJC, Mulder WR, Zaman GJR, Diala I, Eli LD, Lalani AS, Crown J, Collins DM. Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors. Br J Cancer. 2021 Jan 21. doi: 10.1038/s41416-020-01257-x. Epub ahead of print. PMID: 33473169.

2. Conlon NT, Kooijman JJ, van Gerwen SJC, Mulder WR, Zaman GJR, Diala I, Eli LD, Lalani AS, Crown J, Collins DM. Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors. Br J Cancer. 2021 Mar;124(7):1249-1259. doi: 10.1038/s41416-020-01257-x. Epub 2021 Jan 21. PMID: 33473169; PMCID: PMC8007737.

3. Hu D, Lyu X, Li Z, Ekambaram P, Dongre A, Freeman T, Joy M, Atkinson JM, Brown DD, Cai Z, Carleton NM, Crentsil HE, Little J 4th, Kemp F, Klei LR, Beecher M, Sperinde J, Huang W, Joensuu H, Srinivasan A, Pogue-Geile KL, Wang Y, Feng H, Eli LD, Lalani AS, Zou J, Tseng GC, Bruno TC, Lee AV, Oesterreich S, Wolmark N, Allegra CJ, Jacobs SA, McAllister-Lucas LM, Lucas PC. p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2+ breast cancer that limits trastuzumab deruxtecan efficacy. Nat Cancer. 2025 Jun 27. doi: 10.1038/s43018-025-00969-4. Epub ahead of print. PMID: 40579589.